Abstract
Young adults (YA) with non-small cell lung cancer (NSCLC): Snapshot of the oncogenic drivers and immune landscapes
Journal of clinical oncology, Vol.42(16_suppl), pp.8538-8538
06/01/2024
DOI: 10.1200/JCO.2024.42.16_suppl.8538
Abstract
8538 Background: Approximately 5% of NSCLC occurs in patients 50 years or younger (median age:71) representing distinct clinicopathological features. Reports characterizing genomic alterations are scarce. Using a large real-world (RW) dataset, we characterize oncogenic drivers, and immune landscapes to better understand YA with NSCLC. Methods: 42,326 NSCLC specimens were analyzed using next-generation sequencing of DNA (DNA-592 panel or whole exome) or RNA (whole transcriptome) at Caris Life Sciences (Phoenix, AZ). YA (<=50 years) were categorized into three groups (years): 18-30 (A1, n=61), 31-40 (A2, n=277) & 41-50 (A3, n=1,549); vs >50 (A4, n=40,439). Composition of tumor microenvironment (TME) was estimated from bulk RNA sequencing using QuanTIseq method. RW survival on Osimertinib (Osi-OS) was obtained from insurance claims and calculated from initiation of Osi treatment to last contact and was compared between ages 18-50 and >50 years. Hazard ratio (HR) was calculated using the Cox proportional hazards model. Statistical significance was determined using Chi-square, Fisher’s Exact, Mann-Whitney U and log-rank tests and corrected for multiple comparisons where applicable (q<0.05). Results: Consistent with previous reports, NSCLC in YA was more prevalent in females, non-smokers and was associated with adenocarcinoma histology. Among driver alterations, ALK(IHC+), ROS1, RET and NTRK1 fusion were enriched and KRAS mutations were reduced in YA. Interestingly, while the prevalence of KRAS G12D from transition (non-smoker related) and EGFR E746_A750 decreased with age, KRAS G12C from transversion increased with age in YA. YA were also associated with improved Osi-OS (HR: 0.79, median Osi-OS=37.4 months vs 32 months in >50 years old, p=0.019). High tumor mutation burden (>=10 mut/Mb), the prevalence of mutations in TP53, KMT2D, NF1, RBM10, NFE2L2 and NOTCH1 increased while GNAS decreased with age. The expression of immune checkpoint genes such as PDCD1LG2(A1/A4: 0.63, A3/A4: 0.89), LAG3(A2/A4: 0.73, A3/A4: 0.89) and IFNG (A1/A4: 0.32, A3/A4: 0.75) were reduced, while M2 macrophage (A2/A4: 1.2) and neutrophil (A2/A4: 1.2) were increased in YA (all q<0.05). Conclusions: We report an increased prevalence of RET and NTRK1 fusions in YA and key differences in distributions of frequent KRAS and EGFR mutations in YA (vs A4) along with decreased expression of immune related genes in the tumor microenvironment. The implications are under active investigation. [Table: see text]
Details
- Title: Subtitle
- Young adults (YA) with non-small cell lung cancer (NSCLC): Snapshot of the oncogenic drivers and immune landscapes
- Creators
- Aaron Pruitt - University of KentuckyRobert Hsu - University of Southern CaliforniaNishant Gandhi - Caris Life SciencesCoral Olazapasti - University of MiamiEstelamari Rodriguez - Sylvester Comprehensive Cancer CenterDwight Hall Owen - The Ohio State UniversityJinesh Gheeya - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteJun Zhang - University of Kansas Medical CenterMuhammad Furqan - University of IowaJaclyn LoPiccolo - Dana-Farber Cancer InstituteAndrew Elliott - Caris Life SciencesAri VanderWalde - Caris Life SciencesStephanie Rock - Caris Life SciencesPatrick C. Ma - Penn State Milton S. Hershey Medical CenterBalazs Halmos - Montefiore Medical CenterZhonglin Hao - University of Kentucky
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.42(16_suppl), pp.8538-8538
- DOI
- 10.1200/JCO.2024.42.16_suppl.8538
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984651156102771
Metrics
4 Record Views